tbuckley/cabot-search huggingface dataset:
Multi-layered measures for mitigating effects of COVID-19 pandemic on national breast cancer screening programme.
Authors: Miloš Vrhovec, Katja Jarm, Kristijana Hertl, Veronika Kutnar, Vesna Škrbec, Mateja Kurir Borovcic
Journal: Journal of Clinical Oncology (2022)

e22501 Background: The beginning of the COVID-19 pandemic caused a major disturbance in the operation of breast cancer screening programmes worldwide with delays in screening examinations. The 2021 Dutch study Effects of cancer screening restart strategies after COVID-19 disruption describes 4 strategies to reduce the impact of the pandemic on 10-year breast cancer mortality, where a full-catch up strategy with increased screening capacities that allow successful reduction of backlog in 6 months after the restart, was recognized as the most effective. In March 2020, the Slovenian Breast Cancer Screening Programme DORA suspended all screening activities and lost 50 working screening days. When planning the restart of the programme, measures for providing a safe environment with a special protocol were implemented nationwide. The capacity of the programme was increased with measures like working during the summer, additional screening terms and extending working hours. Focus was placed on communication activities to promote a safe screening environment. With centralized planning, invitation letters with prefixed appointment are sent, additionally information about safety measures and a questionnaire were included to enable rescheduling of women with risk factors for COVID-19 infection beforehand. The aim of our study was to compare pre-pandemic and pandemic screening programme quality and activity indicators in order to determine, whether the measures for reducing the impact of the pandemic were effective. Material and Methods: Data for the period 2019–2021 was obtained from the programme's screening registry. Regularly controlled indicators for pre-pandemic and pandemic period were compared. Results: With the full catch-up strategy, screening results in the pandemic period reach the pre-pandemic levels. Conclusions: In Slovenian screening programme it was possible to completely reduce the backlog of screening examinations and achieve indicators’ levels that were observed before the pandemic due to robust screening infrastructure. With the successful implementation of a full catch-up strategy it is expected that the COVID-19 pandemic will not have a significant if any effect on breast cancer mortality in the screening population of Slovenia.[Table: see text]
Prognostic value of vessels encapsulating tumor clusters (VETC) in sarcoma.
Authors: Salvatore Lorenzo Renne, Marta Tassan-Mangina, Ilaria Santori, Laura Ruspi, Federico Sicoli, Piergiuseppe Colombo, Manuela Cammelli, Vittorio Quagliuolo, Luigi Terracciano, Luca Di Tommaso, Ferdinando Cananzi
Journal: Journal of Clinical Oncology (2022)

e23523 Background: How sarcoma metastasize is unknown. VETC has been described as an epithelial-to-mesenchymal-transition independent process of metastasis: endothelium covers neoplastic clusters allowing tumor dissemination. It has also been shown to be a predictive of tyrosine kinase inhibitors (TKI) response. The objectives of the present study are: 1) to assess the presence of VETC in sarcoma; 2) to model its prognostic role. Methods: The study was retrospective. We selected 54 cases of sarcomas (6 DDLPS, 10 GIST, 6 retroperitoneal LMS, 9 MLPS, 8 MPNST, 10 SFT, 5 UPS); of them 31 were metastatic (M1 group), 23 were not (M0 group, defined as least 5 years of negative follow-up). High risk GIST and SFT, and grade 3 FNCLCC were considered high grade. VETC was assessed with CD31 immunohistochemistry and defined as a continuous endothelial lining around tumor clusters. We used Bayesian probabilistic modeling to detect small effects and multilevel hierarchical modeling to reduce overfitting. Models were fit using Stan and R. CI were computed with the HPDI method for 89%. The whole posterior probability (PP) was used for calculations. Results: The two groups (M0 &amp; M1) were substantially homogeneous: the CI of the contrast PP (CPP) included 0 in each histology for sex, age, size, and grade; VETC was more expressed in M1 SFT cases with almost all the CPP mass above the 0. Also, UPS and GIST showed VETC to be more present in metastatic diseases with 79% and 78% respectively of the CPP mass above 0 (see table). Metastasis free survival (MFS) analysis showed that VETC in SFT and UPS with a coefficient of 2.42 (CI 0.73 – 4.65) and 1.94 (CI 0.16 – 3.67); for the latter the median was reached with a PP density of median MFS of 65 months (mo) (standard deviation, SD: 74 mo) for VETC- Vs 11 mo (SD: 14 mo) for VETC+. Similarly, disease specific survival analysis showed – in SFT and UPS – that VETC was negatively associated with prognosis with coefficients of 1.24 and 2.34; however the CI covered slightly the 0 (-0.54 – 3.96 and -0.09 – 5.73, respectively). Conclusions: We found VETC in sarcoma and highlighted its prognostic role in SFT and UPS. [Table: see text]
IMG-08. Response assessment for pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group
Authors: Lindsey M Hoffman, Camilo Jaimes, Kshitij Mankad, David M Mirsky, Benita Tamrazi, Christopher L Tinkle, Cassie Kline, Aparna Ramasubramanian, Fatema Malbari, Ross Mangum, Holly Lindsay, Vincent Horne, David J Daniels, Sameer Keole, David R Grosshans, Tina Young Poussaint, Roger Packer, Sergio Cavalheiro, Brigitte Bison, Todd C Hankinson, Hermann L Müller, Ute Bartels, Katherine E Warren, Murali Chintagumpala
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Craniopharyngioma (CP) is a histologically benign tumor of the pituitary stalk that accounts for 4% of pediatric central nervous system (CNS) tumors. Given its location, CP often causes neuro-endocrine, hypothalamic, and vision dysfunction. Standard therapy consists of maximally safe resection +/- radiation therapy (RT). Medical management, including intra-cystic therapy, may have utility in certain contexts. Survival after CP is excellent, but quality of life is often poor secondary to functional deficits from the tumor and/or treatment. Few prospective CP trials have been performed, and response assessment has not been standardized. METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee, formed of international experts in relevant subspecialties, devised consensus guidelines from published literature and/or expert opinion to assess CP response in prospective clinical trials. RESULTS: Magnetic resonance imaging (MRI) is the recommended radiological modality for baseline and follow-up CP assessment. Computed tomography can be useful for identification of calcification in the initial diagnostic work-up. The committee defined specific standard MRI-based sequences focused on comprehensive evaluation of the suprasellar space. Radiologic CP response is defined by two-dimensional measurements of both solid and cystic tumor components. Three-dimensional measurements are also encouraged in prospective trials. In certain clinical contexts, response of solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment (including transient cyst growth during or after RT). Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into CP response definitions. In most circumstances, cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. CONCLUSION: CP is a common pediatric CNS tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for baseline and longitudinal assessments of CP to uniformly define response in future prospective trials.
Disparities in clinical trial participation in ovarian cancer.
Authors: Anna Jo Bodurtha Smith, Rafael Alvarez, Jonathan Heintz, Fiona Simpkins, Emily Meichun Ko
Journal: Journal of Clinical Oncology (2022)

e18597 Background: Across cancers, significant racial disparities exist in clinical trial enrollment. Our objective was to examine the association of trial enrollment with sociodemographic and health system factors in ovarian cancer. Methods: We conducted a retrospective cohort study of patients with ovarian cancer diagnosed from 2013-2021 using the nationwide de-identified electronic health record-derived Flatiron Health database. We used multi-level regression modeling to analyze the association of clinical trial participation (receipt of a clinical trial drug) with patient, sociodemographic, health system, and cancer factors. Results: Of 8,022 patients with ovarian cancer, 5.0% (95%CI 4.5-5.5) received a clinical drug trial. Medicaid insurance, Hispanic or Latino ethnicity, non-white race, and advanced age were associated with lower trial participation, while residence in the Southeast, advanced-stage, and recurrence were associated with higher participation. Race and insurance disparities persisted in both academic and community settings. Conclusions: In this large cohort study of ovarian cancer, Hispanic/Latino patients and those on Medicaid were significantly less likely to participate in clinical trials. Efforts to increase clinical trial diversity are needed.[Table: see text]
QOL-18. Neuropsychological screening in a pediatric neuro-oncology multidisciplinary clinic.
Authors: Jonathan Mietchen, Alanna Kessler-Jones, Shawn Damodharan, Diane Puccetti
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The purpose of this project was to examine the usefulness of neuropsychological screening in a multidisciplinary clinic for neuro-oncology populations and determine whether a brief evaluation can adequately screen children for cognitive dysfunction or psychiatric comorbidities. METHODS: Thirty-one children or young adults with a history of CNS tumor had neuropsychological screening as part of their multidisciplinary clinic visit. This screening evaluation consisted of clinical interview, neuropsychological testing, and the completion of emotional/behavioral checklists. Our neuropsychological test battery included the Kaufman Brief Intelligence Test-Second Edition (KBIT-2) and the NIH Toolbox Fluid Cognition Composite, which consists of 6 subtests - flanker task, working memory, processing speed, oral reading, card sort, and memory. RESULTS: Over a 15-month period 31 children, adolescents, and young adults with CNS tumors were seen in our neuropsychology screening clinic. Females made up 39% of the sample. The average age was 12.7 years (range=5–24 years). The average time to complete neuropsychological testing was 60.3 minutes. Thirty-six percent did not have any new neuropsychological diagnoses, 42% had one new diagnosis, 19% had two new diagnoses, and 3% had three new diagnoses. The most common new diagnoses were mild or major neurocognitive disorder (mild=29%, major=6%), anxiety (32%), ADHD (10%), and mood disorder (13%). Neurocognitive test scores were mostly in the average range (Verbal-IQ=97.7; Nonverbal-IQ=95.3; Total IQ=96.2; Flanker T-Score=46.1; Working Memory T-Score=44.0; Card Sort T-Score=43.7; Picture Memory T-Score=48.5). Processing speed and fluid cognition composite scores for the group were in the low-average range (Processing Speed T-Score=42.7; Fluid Cognition Composite T-Score=41.4). Behavioral health recommendations were needed for 71% of this sample. Educational recommendations were needed for 58%. CONCLUSIONS: Brief neuropsychological screening completed as part of multidisciplinary clinics for pediatric neuro-oncology patients was efficient and useful in identifying neuropsychological diagnoses in children and assisted with informing necessary behavioral health and academic interventions.
New perspectives on an old grouping: The genomic and phenotypic differences of Oxalobacter formigenes
Authors: J.A. Chmiel, R. Venema, C. Carr, K.F. Al, R.M. Chanyi, S. Ari Domínguez Romero, G.A. Stuivenberg, H. Razvi, J. Bjazevic, J.P. Burton
Journal: European Urology (2022)
A phase 1 study of ADI-001: Anti-CD20 CAR-engineered allogeneic gamma delta (γδ) T cells in adults with B-cell malignancies.
Authors: Sattva Swarup Neelapu, Mehdi Hamadani, David Bernard Miklos, Houston Holmes, John Hinkle, Jackie Kennedy-Wilde, Ori Maller, Maggie Weinstein, Francesco Galimi, Rose Lai, Don A. Stevens
Journal: Journal of Clinical Oncology (2022)

7509 Background: ADI-001 is a first-in-class allogeneic gamma delta (γδ) CAR T-cell therapy targeting the B-cell antigen CD20. ADI-001 also has both adaptive and innate cytotoxic effector functions to complement CAR targeting, potentially enhancing efficacy and reducing the possibility of tumor escape due to antigen loss. ADI-001 expresses MHC independent γδ T cell receptors, thus lowering the risk of graft versus host disease (GvHD) without the need for gene-editing. Methods: This phase 1 trial evaluates ADI-001 in adults with relapsed/refractory advanced B-cell lymphoma. Eligibility criteria included presence of measurable lesions, expression of CD20 and ≥ 2 prior systemic therapies. All patients received conditioning therapy with fludarabine and cyclophosphamide. ADI-001 is administered at 3 flat dose levels (DL; DL1:3E7, DL2:1E8, or DL3:3E8 cells) in a 3 + 3 dose-escalation scheme. Dose-limiting toxicities (DLT) were monitored during the initial 28-days post-treatment. Patients who completed the 28-day DLT period were considered evaluable. Treatment-emergent adverse events were graded by CTCAE v5.0, and immune effector cell toxicity assessment and grading were performed per ASTCT criteria. Objective response rates (ORR) were evaluated by independent radiographic review per Lugano 2014 criteria. Results: As of 14 February 2022, eight patients were enrolled and six were evaluable. Of these six patients, 2/6 were female (33%) and the median age was 62 years (range 45-75). The median number of prior therapies was 3.5 (range 2-5) and median IPI score was 3.5 (range 2-4). One patient received prior anti-CD19 CAR T cells therapy with lisocabtagene maraleucel. There were five patients with large B-cell lymphoma and one with mantle cell lymphoma. Among the six evaluable patients, three were treated on DL1 and three on DL2. Most related AEs (78%) were of grade 1/2. There were three AESI: two CRS (one grade 1 and one grade 2) and one grade 1 ICANS, and the only related SAEs were the grade 2 CRS and grade 1 ICANS. There was no reported GvHD and no protocol defined DLT events. At day 28, the ORR based upon PET/CT was 67% (4/6 patients) and the CR rate was 67% (4/6 patients). Both patients with ≥ 3 months post-treatment follow-up remained in CR. Additional data will be presented at the meeting. Conclusions: ADI-001 γδ CAR T cells were well tolerated, with a favorable safety profile and encouraging preliminary efficacy. Patients who achieved CR at day 28 appeared to be disease free during further follow-up at month-3. Clinical trial information: NCT04735471.
Reducing oncology readmissions through a multidisciplinary discharge approach.
Authors: Samantha DiBenedetto, Eric Pierce, Leah Wells, Michael Kenneth Keng
Journal: Journal of Clinical Oncology (2022)

6561 Background: Hospital readmissions are associated with increased health care utilization and unfavorable patient outcomes. Oncology patients have an increased risk of hospital readmission compared to the general patient population. The 30-day readmission rate for cancer patients at our institution is 27.7% which is higher than the reported national average of 20.2%. We sought to reduce 30-day hospital readmission rates by 25% for solid tumor oncology patients through a prospective integrated multidisciplinary discharge approach. Methods: Hospital readmissions for adult patients with a known solid tumor cancer diagnosis admitted to the oncology service at UVA from Jan 2019 – Apr 2019 were identified. Baseline information on tumor type, reason for readmission, interventions, length of stay (LOS), and inpatient morbidity and mortality (including ICU admission and transition to hospice) were collected via retrospective review. Qualitative and quantitative tools including process maps, cause-and-effect diagrams, Pareto charts, and priority matrix were used to identify potential areas for intervention. Two PDSA cycles were implemented: daily multidisciplinary discharge rounds with physicians, nursing, social work, case management, and PT/OT (PDSA1), and a templated discharge email to patients’ primary oncology team including attending oncologist, mid-level providers, nurse coordinator, pharmacist, and urgent care team (PDSA2). An SPC chart with 3-σ limits and t-test of unequal variance with 2-sided p-value was used to evaluate impact on readmission rates from baseline to PDSA2. Results: Following PDSA1 (May 2019 – Oct 2019), the 30-day readmission was 25.7%; PDSA2 was postponed due to COVID-19, however the 30-day readmission rate remained stable during the pandemic. Following PDSA2 (Sept 2021 – Dec 2021), the 30-day readmission rate was 18.2% corresponding to an absolute decrease of 34.3% which was statistically significant (p≤0.05). This was associated with a trend towards increased LOS, rate of ICU admission, and case-mix severity index although not statistically significant. There was no significant difference in inpatient mortality or transition to hospice (Table). Conclusions: Implementation of multidisciplinary discharge rounds and templated discharge communication resulted in a significant decrease in rate of 30-day readmissions for solid tumor oncology patients. There was a trend towards increased LOS and ICU admissions without increased inpatient mortality. Improvement in discharge email compliance and implementation of an urgent symptom clinic may further reduce the 30-day readmission rate. [Table: see text]
Major stressful events and risk of developing head/neck and pancreatic cancer.
Authors: Arthi Sridhar, Chandler H. Nguyen, Kamelah Abushalha, Iqra Saghir, Amirali Tahanan, Mohammad Hossein Rahbar, Syed Hasan Raza Jafri
Journal: Journal of Clinical Oncology (2022)

12128 Background: Major stressful life events have been shown to be associated with an increased risk of lung cancer, breast cancer and the development of various chronic illnesses. The stress response generated by our body results in a variety of physiological and metabolic changes which can affect the immune system, endocrine system and metabolism which has been shown to be associated with tumor progression. There is an indication that stress may need to be considered as a risk factor for malignancies. Methods: This is a matched case control study. The objective of this study was to determine if major stressful life events are associated with the incidence of head, neck, and pancreatic cancer (HNPC). Cases (CA) were HNPC patients diagnosed within the previous 12 months. Controls (CO) were patients without a prior history of malignancy and were matched with the cases by age and smoking status. Basic demographic data and medical information were collected from the patient’s medical records. Data on major stressful life events were collected using the modified Holmes-Rahe stress scale, and the following variables: death of a spouse, death of a child/immediate family member, serious personal illness, divorce/separation, loss of a job, caring for ill family member, financial difficulties, relocation, stress at work, detention/incarceration and retirement. A total sample of 300 was needed (100 cases, 200 controls) to achieve at least 80% power to detect odds ratios (OR) of 2.00 or higher at 5% level of significance. Results: From January 2018 to August 2021, 278 patients were enrolled (CA = 77, CO = 201) matched for mean age (years) (CA = 63, CO = 64), median smoking exposure (years) (CA = 36, CO = 38). About 65% of patients in CA group and 49% of CO group were male and 54% and 46% of the CA and CO groups respectively were of white race. In a multivariable logistic regression analysis after controlling for potential confounding variables (including sex, age, race, education, marital status, smoking history), there was no difference in lifetime incidence of major stressful event between the cases and controls. However, patients with HNPC were significantly more likely to report a major stressful life event within past 5 years when compared to CO [OR = 2.59 (1.24, 5.44), p = 0.012]. Conclusions: Patients with head, neck and pancreatic cancers are significantly associated with having a major stressful life event within 5 years of their diagnosis. This study highlights the potential need to recognize stressful life events as risk factors for developing malignancies and consider incorporating early rehabilitative efforts for major life stressful events.
How important are morphologic subtypes on the prognosis of surgically treated non-metastatic papillary renal cell carcinoma? An analysis from a contemporary multi-institutional database
Authors: S. Erdem, U. Capitanio, R. Campi, D. Amparore, M. Carme Mir, E. Roussel, N. Pavan, O. Kara, T. Klatte, E. Degirmenci, R. Aydin, A. Minervini, S. Serni, A. Berni, R. Giacomo, F. Ozcan
Journal: European Urology (2022)
FLEX, the 30,000 breast cancer transcriptome project: A platform for early breast cancer research using full-genome arrays paired with clinical data.
Authors: Cynthia X. Ma, Pat W. Whitworth, Svetislava J. Vukelja, Carl R. Gray, Sami Diab, Jennifer Crozier, Julian Berrocal, Mehran Habibi, Adam Brufsky, Robert Maganini, Gordan Srkalovic, Manojkumar Bupathi, Trevor Feinstein, Joyce O'Shaughnessy, Julie Barone, Esther Hoogland Rehmus, Laura A. Lee, Holly Nguyen, Lisa Eileen Blumencranz, M. William Audeh
Journal: Journal of Clinical Oncology (2022)

TPS612 Background: The ongoing, multi-center FLEX trial (NCT03053193) began in the United States in 2017, with the ultimate goal of 30,000 patients enrolled. The primary objective is to create a large-scale collaborative registry of early-stage breast cancer patients that links comprehensive clinical and full genome expression data to reveal new prognostic and/or predictive gene signatures. A key secondary objective of the trial is to enable investigator-initiated studies to explore early-stage breast cancer at a relatively low cost to the investigator. Methods: The prospective FLEX trial enrolls patients aged ≥ 18 years with histologically proven stage I-III breast cancer, with negative or 1-3 positive lymph nodes. Eligible patients have received MammaPrint, with or without BluePrint testing as standard of care, and consent to clinically annotated full transcriptome data collection. The FLEX base study protocol permits investigators to submit their own concept proposal, and upon review and approval by the Research and Scientific Review Committees, investigators interrogate clinical and genomic data from the FLEX database. The 10-year enrollment goal is a minimum of 30,000 patients. Since April 2017, 9,170 patients have been enrolled at over 109 sites in the United States. To date, 38 investigator-initiated substudies have been approved and are in progress, and 28 abstracts have been published in the US scientific congresses. To ensure inclusion of diverse populations, patients from local communities and 11 National Cancer Institute-designated Comprehensive Cancer Centers were included. Our diverse data set is helping meet the needs of historically under-represented patients with breast cancer. Of the self-reported ethnicities within the FLEX database, 65% are White or Caucasian, 8% Black or African American, 4% Latin American, and 2% Asian. There are 5 ongoing FLEX sub studies investigating racial disparities. The molecular profiling and differential gene expression analysis in early-stage breast cancer patients of African American, Asian, Hispanic ancestries helps to provide critical insights that correlate tumor biology with treatment outcomes. FLEX is expanding globally with sites anticipated in multiple European countries. The FLEX trial continues to expedite the discovery and development of novel genomic profiles, bringing precision oncology into the clinic to improve breast cancer management. Clinical trial information: NCT03053193.